Embryo attachment to the uterine epithelium (UE) is a dynamic example of cell-cell interactions. This process is regulated both by the developmental program of the embryo and the steroid hormone influences on the uterus. Recent work from our laboratory indicates that in mice HS (HS) proteoglycans of embryonic and UE cell surfaces interact with novel complementary HS receptors of the UE cell surface during implantation. Furthermore, evidence from a variety of systems, indicate that HS and HS- binding proteins not only strongly influence cell adhesion, but also a number of cellular responses to growth factors as well as patterns of gene expression. Given the importance of HS in embryo implantation, in particular, and in cellular responses, in general, it is of great biological interest to characterize the receptors that mediate cellular interactions with HS. This proposal describes studies to characterize HS receptors expressed on the cell surface of mouse UE cells and human UE cell lines. A variety of biochemical and cell biological approaches will be taken to determine the structural features of HS required for receptor binding, the structural features of the HS receptors themselves and the functions of HS receptors in embryo adhesion and signal transmission. Collectively, these studies will characterize molecular and functional aspects of a novel class of cellular receptors for extracellular matrix components involved in embryo- uterine interactions.